Intravenous combined with aerosolised polymyxins versus intravenous polymyxins monotherapy for ventilator-associated pneumonia: a systematic review and meta-analysis

Polymyxins was applied to treat ventilator associated pneumonia (VAP) caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) via different administration routes. The potential benefits of aerosolised polymyxins as adjunctive treatment for patients still were contradictory. This review assessed the safety and efficacy of intravenous combined with aerosolised polymyxins versus intravenous polymyxins monotherapy in patients with VAP caused by CR-GNB. Two reviewers independently evaluated and extracted date from Pubmed, Embase, Cochrane library and Web of science. The primary outcome was all-cause mortality and secondary outcomes included clinical cure rate, clinical improvement rate, microbiological eradication and nephrotoxicity. Differences for dichotomous outcomes were expressed as odds ratios (OR) with 95% confidence intervals (CI). Eleven eligible studies were included. The results showed that compared with intravenous polymyxins monotherapy, intravenous plus aerosolised polymyxins therapy significantly reduced all-cause mortality rate (OR = 0.75, 95% CI 0.57 - 0.99, P = 0.045) and improved clinical improvement rate (OR = 1.62, 95% CI 1.02 - 2.60, P = 0.043) and microbial eradication rate (OR = 2.07, 95% CI 1.40 - 3.05, P = 0.000). However, there were no significant difference in terms of clinical cure rate (OR = 1.59, 95% CI 0.96 - 2.63, P = 0.072) and nephrotoxicity (OR = 1.14, 95% CI 0.80 - 1.63, P = 0.467) for intravenous plus aerosolised polymyxins therapy. Subgroup analysis revealed that the clinical improvement rate was improved significantly in case-control studies. Aerosolised polymyxins maybe a useful adjunct to intravenous polymyxins for CR-GNB VAP patients.